CN113092624A - Ruidexiwei-related substance and content determination method - Google Patents
Ruidexiwei-related substance and content determination method Download PDFInfo
- Publication number
- CN113092624A CN113092624A CN202110373152.6A CN202110373152A CN113092624A CN 113092624 A CN113092624 A CN 113092624A CN 202110373152 A CN202110373152 A CN 202110373152A CN 113092624 A CN113092624 A CN 113092624A
- Authority
- CN
- China
- Prior art keywords
- concentration
- solution
- content
- sample
- reidesciclovir
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/30—Control of physical parameters of the fluid carrier of temperature
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed
- G01N2030/324—Control of physical parameters of the fluid carrier of pressure or speed speed, flow rate
Abstract
The invention relates to preparation of Reidesvir, in particular to a Reidesvir related substance and a content determination method, which comprises the following steps of a, preparing a standard solution, weighing a Reidesvir reference substance, and preparing the standard solution; b, preparing a sample solution, namely weighing a Dericoxi sample to be tested, and preparing a high-concentration sample solution and a low-concentration sample solution; c, injecting a high-concentration test sample solution, and calculating the content of impurities by selecting an area normalization method; and d, injecting a standard solution and a low-concentration test solution, calculating the content of the Reidcisvir by an external standard method, realizing complete separation of the Reidcisvir and impurities without gradient elution, wherein the minimum separation degree is more than 1.2, and effectively avoiding interference among the impurities.
Description
Technical Field
The invention relates to preparation of Reidesciclovir, in particular to a Reidesciclovir related substance and a content determination method.
Background
Reddeivir (Remdesivir), a viral RNA-dependent RNA polymerase (RdRp) inhibitor developed by Gilead Science, Gilidd sciences. The antiviral drug Reidevir approved by the United states Food and Drug Administration (FDA) for Jilide science is used for treating Xinguan inpatients in 22/10/2020, and becomes the first officially approved Xinguan therapeutic drug in the United states. The CAS registry number of the Reidesciclovir is 1809249-37-3, the molecular formula is C27H35N6O8P, molecular weight of 602.58, is named 2-ethylbutylN- { (S) - [2-C- (4-aminopyrrolo [2,1-f ]][1,2,4]triazin-7-yl)-2,5-anhydro-d-altrononitril-6-O-yl]The phenoxyphosphoryl } -L-alaninate has the chemical structure of,
the method is characterized in that the Reidesciclovir is used as a raw material medicine, the impurity content and the Reidesciclovir content of the Reidesciclovir are required to be accurately measured in the fields of analytical chemistry and pharmaceutical analysis, some impurities cannot be completely removed in the preparation process, components need to be identified, high performance liquid chromatography can accurately separate and detect compounds, and the method for detecting the Reidesciclovir components by means of the high performance liquid chromatography is researched.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a Reidesciclovir related substance with simple operation and high detection precision and a content determination method.
The invention is realized by the following technical scheme: a method for measuring related substances of Reidesciclovir and content thereof, which comprises the following steps,
a, preparing a standard solution, and weighing a Rudexiluwei reference substance to prepare the standard solution;
b, preparing a sample solution, and weighing a Reidcciclovir sample to prepare a high-concentration sample solution and a low-concentration sample solution;
c, injecting a high-concentration test sample solution, and calculating the content of impurities by selecting an area normalization method;
and d, injecting a standard solution and a low-concentration sample solution, and calculating the content of the Redexilvir by an external standard method.
Further, the concentration of the RudeSeviru reference substance in the standard solution is 2.00-11.98 mu g/ml.
Further, the concentration of the Reidesciclovir test sample in the high-concentration test sample solution is 0.9-1.1 mg/ml.
Furthermore, the concentration of the Reidesciclovir test sample in the low-concentration test sample solution is 2.0-11.98 mu g/ml.
Further, the mobile phase selected in the step a and the step b is composed of 0.05% trifluoroacetic acid aqueous solution and methanol, and the volume ratio of the 0.05% trifluoroacetic acid aqueous solution to the methanol is 2: 3.
Further, the column temperature of the chromatographic column in the reversed phase high performance liquid chromatography is 20-25 ℃.
Furthermore, the detector in the reversed-phase high performance liquid chromatography is an ultraviolet detector, and the detection wavelength is 250-260 nm.
Further, the flow rate in the reversed-phase high-performance liquid chromatography was 1.0ml/min, and the amount of the sample was 20. mu.l.
Furthermore, the analysis time for measuring the impurity content of the high-concentration test solution is 56-63 min.
Furthermore, the analysis time for determining the content of the Rudexiluwei in the low-concentration test solution and the standard solution is 18-23 min.
The invention has the beneficial effects that: the method is used for detecting the impurity content of the Reidesciclovir and the content of the Reidesciclovir based on the high performance liquid chromatography, has high detection precision and simple operation, realizes the complete separation of the Reidesciclovir and the impurities without gradient elution, has the minimum separation degree of more than 1.2, and effectively avoids the interference among the impurities.
Drawings
FIG. 1 is a test sample spectrum for impurity determination of Reidesvir in example 1;
FIG. 2 is a graph of the test sample for determining the content of Reidesciclovir in example 1;
fig. 3 is a graph of the linear relationship of the content measurement of the Reidesciclovir of example 1.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the following examples:
the RudeSewei reference substance is obtained by self-making, and the content of the RudeSewei is more than 97.0 percent;
the methanol is chromatographically pure, the trifluoroacetic acid is analytically pure, and the water is purified water;
the high performance liquid chromatograph is Shimadzu SPD-10Avvp type high performance liquid chromatograph, the chromatographic column is C18 silane bonded silica gel packed chromatographic column, the detector is ultraviolet detector, the detection wavelength is 254nm, the inner diameter of the chromatographic column is 4.6mm, the length is 150mm, and the filler particle size is 5 μm;
the mobile phase selected in the step a and the mobile phase selected in the step b both consist of trifluoroacetic acid aqueous solution with mass concentration of 0.05% and methanol, and the volume ratio of the 0.05% trifluoroacetic acid aqueous solution to the methanol is 2: 3;
the flow rate in the reversed phase high performance liquid chromatography is 1.0ml/min, and the sample injection amount is 20 ul;
the analysis time for measuring the impurity content of the high-concentration test solution is 60 min;
the analysis time for measuring the content of the RudeSewei in the low-concentration test solution and the standard solution is 20 min.
Weighing both the Rudexiluwei reference substance and the Rudexiluwei test substance by using an analytical balance, in particular to a Mettler-Toriledo MS105DU type analytical balance.
Step a, preparing a standard solution, weighing a Rudexiwei reference substance, and preparing the standard solution, specifically, weighing 20mg of the Rudexiwei reference substance, putting the Rudexiwei reference substance into a 20ml measuring flask, adding a mobile phase for dissolving and diluting to a scale to obtain a standard solution to be diluted, measuring 1ml of the standard solution to be diluted, putting the standard solution into a 100ml measuring flask, diluting to the scale by using the mobile phase, shaking up to obtain the standard solution, wherein the content of the Rudexiwei reference substance in the standard solution is 10 mu g/ml;
in the step b, the preparation method of the high-concentration test solution comprises the steps of taking 20mg of the Reidcisvir test sample, placing the Reidcisvir test sample in a 20ml measuring flask, adding the mobile phase for dissolving, diluting to a scale, shaking up to obtain the high-concentration test solution, wherein the content of the Reidcisvir test sample is 1 mg/ml;
in the step b, the preparation method of the low-concentration test solution comprises the steps of taking 20mg of the Reidesciclovir sample, placing the Reidesciclovir sample in a 20ml measuring flask, adding the mobile phase for dissolving and diluting to the scale to obtain the low-concentration test solution to be diluted, shaking up to obtain the high-concentration test solution, taking 1ml of the low-concentration test solution to be diluted, placing the low-concentration test solution in a 100ml measuring flask, diluting to the scale by the mobile phase, shaking up to obtain the low-concentration test solution, wherein the content of the Reidesciclovir sample in the low-concentration test solution is 10 mu g/ml.
In steps C-d, the chromatographic column used was Agilent ZORBAX Eclipse XDB-C18, size 4.6mm X150 mm, 3.5 μm; the mobile phase was 0.05% trifluoroacetic acid water-methanol; the detection wavelength is 254 nm; the flow rate is 1.0 ml/min; the injection volume is 20 mul; the running time is 60min, and automatic sample injection is carried out.
The applicant researches and discovers that the concentration of a standard solution is prepared according to about 10 mu g/ml, the concentration of the prepared standard solution can fluctuate, 9 mu g/ml-11 mu g/ml is applicable, and linear and range tests show that the concentration and the peak area of the Reidexi Wevir are in a linear relation in a concentration range of 2.00 mu g/ml-11.98 mu g/ml, namely in a concentration range of 2.00 mu g/ml-11.98 mu g/ml, and the results of the Reidexi Wevir content measurement are reliable.
The high-concentration test solution is prepared according to about 1mg/ml, the concentration of the prepared high-concentration test solution can fluctuate, 0.9mg/ml to 1.1mg/ml can be obtained, and impurities with the content of 0.003 percent can be detected at the concentration, so that the sensitivity is high.
Trifluoroacetic acid is added to adjust the pH of the eluent, the trifluoroacetic acid is used as an ion pair reagent to interact with the Reidesvir, the separation effect can be enhanced, the sample peak shape is better, when the ratio is selected to be 2:3, the retention time of the Reidesvir peak is 9-10min, and the separation degree of the Reidesvir peak and the impurity peak meets the requirement.
Particularly, in the detection process, the temperature is 25 ℃, the room temperature is 25 ℃ for testing, and the durability is good under the temperature condition through verification.
Example 1
A method for measuring related substances of Reidesciclovir and content thereof, which comprises the following steps,
preparing a standard solution, weighing a Rudeseivir reference substance, and preparing the standard solution;
b, preparing a sample solution, and weighing a Reidcciclovir sample to prepare a high-concentration sample solution and a low-concentration sample solution;
c, injecting a high-concentration test sample solution, and calculating the content of impurities according to an area normalization method;
and d, injecting a standard solution and a low-concentration test solution, and calculating the content of the Reidcisvir by peak area according to an external standard method.
The detection chromatogram obtained in the step c is shown in figure 1, the standard solution detection chromatogram obtained in the step d is shown in figure 2, as can be seen from figure 1, the retention time of the main peak of the ridciclovir is 9.411min, the peak shape is good, the tailing factor is 1.502, the ridciclovir and the impurities can be completely separated, and the minimum separation degree is more than 1.2;
from fig. 2, it can be seen that the retention time of the reidsivir main peak is 9.792min, the peak shape is good, the tailing factor is 1.324, and the theoretical plate number is 5890.
During detection, attention needs to be paid to influence of the room temperature on the retention time of the main peak, when the room temperature is lower, the retention time of the main peak is later, and when the room temperature is higher, the retention time of the main peak is earlier.
The results of the validation tests were carried out,
1. the system adaptability of the reed-seivir component detection method provided in embodiment 1 is verified.
Repeating the step d6 times, wherein the detection results are shown in the attached table 1.
Attached table 1
The method can be obtained from the attached table 1, the same Reidesvir reference solution is repeatedly added for 6 times, the RSD% of the Reidesvir peak area is 0.42%, and the RSD% in pharmacopoeia is less than 2.0%, so that the applicability of the Reidesvir component detection method system provided by the invention is good.
The detection results of different column temperatures are shown in the attached table 2.
Attached table 2
| Condition | Unknown impurity 1 | Unknown impurity 2 | Unknown impurity 3 | Ruidexiwei (Ridexil) |
| Column temperature 25 deg.C | 0.03％ | 0.36％ | 0.48％ | 99.8 |
| Column temperature | ||||
| 20 deg.C | 0.03％ | 0.37％ | 0.47％ | 100.3 |
| Column temperature | ||||
| 30 deg.C | 0.03％ | 0.37％ | 0.48％ | 99.8％ |
As can be seen from the attached Table 2, the detection is stable and the reliability is high in the environment of 25 ℃.
The results of the different flow measurements are shown in the attached Table 3.
Attached table 3
| Condition | Unknown impurity 1 | Unknown impurity 2 | Unknown impurity 3 | Ruidexiwei (Ridexil) |
| Flow rate 1.0ml/min | 0.03％ | 0.36％ | 0.48％ | 99.8％ |
| Flow rate 0.9ml/min | 0.04％ | 0.36％ | 0.48％ | 100.1％ |
| Flow rate 1.1ml/min | 0.03％ | 0.36％ | 0.48％ | 100.0％ |
As can be seen from the attached Table 3, under the condition of the flow rate of 0.9-1.1ml/min, the change of the detection result is not obvious, and the influence of the flow rate on the detection is not great.
The analysis time of the impurity content is 60min, and according to a typical map, an impurity peak appears at 45.146min, no impurity peak appears at the back, and the selection for 60min is more appropriate. It is also known from durability that 60min is suitable, and the results are shown in the following Table 4.
Attached table 4
| Condition | Final impurity peak retention reagent |
| Original conditions | 45.146 |
| Column temperature | |
| 20 deg.C | 46.914 |
| Column temperature | |
| 30 deg.C | 46.998min |
| Flow rate 0.9ml/min | 50.613min |
| Flow rate 1.1ml/min | 38.141min |
The column temperature is 25 ℃, the flow rate is 1.0ml/min, the detection wavelength is 254nm, the sample injection volume is 20 mul, the common parameters are selected, the change of the column temperature and the detection wavelength has no influence on the detection, the change of the flow rate can influence the retention time of the main peak, the sample injection volume is a fixed value, and the durability result of the impurity content is shown in the attached table 5.
Attached table 5
The durability results of the reed-seivir assay are shown in table 6.
Attached table 6
2. The linear range of the reed-seivir component detection method provided in example 1 was verified.
According to the preparation method for preparing the low-concentration test solution, serial Reidesvir linear solutions with the test contents of 2.00 mu g/ml, 4.99 mu g/ml, 7.98 mu g/ml, 9.98 mu g/ml and 11.98 mu g/ml are prepared, the steps c-e6 are repeated, a chromatogram is recorded, the concentration of Reidesvir is used as a horizontal coordinate, the peak area is used as a vertical coordinate, linear regression is carried out by using a least square method, and the test result is shown in figure 3.
The linear regression equation obtained by the calculation of standard curve data is that y is 21500.2979x +2065.1998, the linear correlation coefficient r is 0.9999, r is more than or equal to 0.999 according to the pharmacopoeia regulation, and the linear relation of the Reidesciclovir within the range of 2.00-11.98 mug/ml is good.
3. The repeatability of the detection method of the components of the reed-solomon provided in example 1 was verified.
As already described above, in step b, the preparation method of the high-concentration test solution includes taking 20mg of the ridciclovir sample, placing the ridciclovir sample in a 20ml measuring flask, adding the mobile phase for dissolution, diluting to a scale, shaking uniformly to obtain the high-concentration test solution, wherein the content of the ridciclovir sample is 1mg/ml, preparing the high-concentration test solution by respectively weighing 20.00mg, 20.04mg, 20.13mg, 19.88mg, 20.06mg and 19.96mg of the ridciclovir sample, detecting according to the method for detecting the components provided in example 1, and determining the content of each test solution as shown in attached table 7.
Attached table 7
The result shows that the average content of the raw material of the RudeSewei is 99.8 percent, the content RSD percent is 0.37 percent, the regulation in pharmacopoeia is met, the regulation is specifically that when the content of the component to be measured is 100 percent, the RSD percent is not more than 1.0 percent, and the repeatability of the component detection method of the RudeSewei is good.
4. The recovery rate of the detection method of the components of the reed-solomon provided in example 1 was verified.
The method uses the RudeSeviru reference substance and the RudeSeviru raw material to prepare three investigation samples with different concentrations, namely low, medium and high concentrations, and performs parallel 3 times of measurement according to the method provided by the invention, and records chromatograms, wherein the recovery rate, the average recovery rate and the RSD value obtained by the measurement result are shown in the attached table 8.
Attached table 8
As can be seen from the attached Table 8, the results show that the recovery rate is 98.49-100.29%, the RSD% is 0.69%, the method conforms to the regulations in pharmacopoeia, specifically, when the content of the components is determined to be 100%, the recovery rate limit is 98-101%, and the RSD% is not more than 2.0%, which indicates that the accuracy of the Rudexilvir component detection method is good.
5. The stability of the detection method of the components of the reed-solomon provided in example 1 was verified.
Preparing low-concentration test solution, placing at 5 ℃, sampling at 0, 13, 19 and 30 hours respectively, carrying out sample injection measurement according to the method of the invention, recording a chromatogram, and calculating an RSD value according to the area of the peak of the Reidesciclovir as shown in the attached table 9.
Attached watch 9
The result shows that the area RSD% of the Reidesciclovir peak is 0.42%, which indicates that the Reidesciclovir component detection method has good stability.
6. The quantitative limit and the detection limit of the method for detecting the components of the reed-seivir provided in example 1 were verified.
The ratio (signal-to-noise ratio, S/N) of the peak height of the RudeSevere to the baseline noise in the chromatogram is about 3, as shown in figure 2, the detection limit of the method for detecting the RudeSevere component provided by the invention is 0.03 mu g/ml;
the ratio (signal-to-noise ratio, S/N) of the peak height of the RudeSevere to the baseline noise in the chromatogram is about 10 as a quantitative standard, and as shown in figure 2, the detection limit of the method for detecting the RudeSevere component is 0.10 mu g/ml.
The results of the 1-6 verification shows that the detected content of the Reidesciclovir provided by the invention presents a good linear relation in the range of 2.00-11.98 mug/ml, the regression equation is 21500.2979x +2065.1998, the correlation coefficient r is 0.9999, the precision, repeatability and accuracy are good, the method is simple, the content measurement is accurate and reliable, no peak occurs, the detection result is good, and the Reidesciclovir component detection method can be used for content measurement of Reidesciclovir test samples.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.
Claims (10)
1. A Reidesciclovir related substance and a content determination method thereof are characterized by comprising the following steps,
a, preparing a standard solution, and weighing a Rudexiluwei reference substance to prepare the standard solution;
b, preparing a sample solution, and weighing a Reidcciclovir sample to prepare a high-concentration sample solution and a low-concentration sample solution;
c, injecting a high-concentration test sample solution, and calculating the content of impurities by selecting an area normalization method;
and d, injecting a low-concentration sample solution, and calculating the content of the Redexilvir by an external standard method.
2. A ridciclovir-related substance and a content determination method according to claim 1, wherein the concentration of the ridciclovir reference substance in the standard solution is 2.00-11.98 μ g/ml.
3. A Reidesciclovir-related substance and a content determination method according to claim 1, wherein the concentration of the Reidesciclovir sample in the high-concentration sample solution is 0.9-1.1 mg/ml.
4. A Reidesciclovir-related substance and a content determination method according to claim 1, wherein the concentration of the Reidesciclovir sample in the low-concentration sample solution is 2.0-11.98 μ g/ml.
5. A reidecivir related substance and content determination method according to claim 1, wherein the mobile phase used in step a and step b is composed of 0.05% trifluoroacetic acid aqueous solution and methanol, and the volume ratio of the 0.05% trifluoroacetic acid aqueous solution to the methanol is 2: 3.
6. A Rudeciclovir relating substance and its content measuring method according to claim 1, characterized in that the temperature of chromatographic column in reversed phase high performance liquid chromatography is 20-25 ℃.
7. The method for determining the content of the Reidesciclovir related substance as claimed in claim 1, wherein the detector in the reversed-phase HPLC is an ultraviolet detector, and the detection wavelength is 250-260 nm.
8. A Rudeciclovir relating substance and its content measuring method according to claim 1, wherein the flow rate in reversed phase high performance liquid chromatography is 1.0ml/min, and the sample amount is 20 μ l.
9. A Rudeciclovir relating substance and its content measuring method, as claimed in claim 1, wherein the analysis time for measuring the impurity content in the high concentration test solution is 56-63 min.
10. A method for determining contents of related substances in reed-solomon according to claim 1, wherein the analysis time for determining the contents of the reed-solomon in the low-concentration test solution and the standard solution is 18 to 23 min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110373152.6A CN113092624A (en) | 2021-04-07 | 2021-04-07 | Ruidexiwei-related substance and content determination method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110373152.6A CN113092624A (en) | 2021-04-07 | 2021-04-07 | Ruidexiwei-related substance and content determination method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113092624A true CN113092624A (en) | 2021-07-09 |
Family
ID=76674625
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110373152.6A Pending CN113092624A (en) | 2021-04-07 | 2021-04-07 | Ruidexiwei-related substance and content determination method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113092624A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200237689A1 (en) * | 2018-11-15 | 2020-07-30 | Bluewillow Biologics, Inc. | Prevention and treatment of coronavirus and other respiratory infections using nanoemulsion compositions |
| CN111679010A (en) * | 2020-06-20 | 2020-09-18 | 盐城师范学院 | High performance liquid chromatography detection method for Ruideciclovir intermediate GS-441524 |
| CN111766317A (en) * | 2020-07-02 | 2020-10-13 | 盐城师范学院 | Method for measuring GS-441524 content in preparation by using polyethylene glycol and water |
| CN111961079A (en) * | 2020-07-17 | 2020-11-20 | 南京正济医药研究有限公司 | Ruideciclovir related substance and preparation method and application thereof |
| CN112358504A (en) * | 2020-09-28 | 2021-02-12 | 南京正济医药研究有限公司 | Ruidexiwei related substance and preparation method and application thereof |
-
2021
- 2021-04-07 CN CN202110373152.6A patent/CN113092624A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200237689A1 (en) * | 2018-11-15 | 2020-07-30 | Bluewillow Biologics, Inc. | Prevention and treatment of coronavirus and other respiratory infections using nanoemulsion compositions |
| CN111679010A (en) * | 2020-06-20 | 2020-09-18 | 盐城师范学院 | High performance liquid chromatography detection method for Ruideciclovir intermediate GS-441524 |
| CN111766317A (en) * | 2020-07-02 | 2020-10-13 | 盐城师范学院 | Method for measuring GS-441524 content in preparation by using polyethylene glycol and water |
| CN111961079A (en) * | 2020-07-17 | 2020-11-20 | 南京正济医药研究有限公司 | Ruideciclovir related substance and preparation method and application thereof |
| CN112358504A (en) * | 2020-09-28 | 2021-02-12 | 南京正济医药研究有限公司 | Ruidexiwei related substance and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| SAWITTREE SAHAKIJPIJARN等: "Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing", 《PHARMACEUTICS》 * |
| 张芬等: "瑞德西韦的合成方法", 《中国药业》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111766317B (en) | Method for measuring GS-441524 content in preparation by using polyethylene glycol and water | |
| CN111855881B (en) | Method for detecting hydroxylamine hydrochloride in azilsartan | |
| WO2023124924A1 (en) | Method for detecting residual solvent in pingyangmycin hydrochloride bulk drug | |
| CN115060832B (en) | Method for detecting contents of oxcarbazepine and preservatives in oxcarbazepine oral suspension | |
| CN115453012A (en) | Reverse phase HPLC method for simultaneously determining multiple positional isomers in vortioxetine hydrobromide | |
| CN114994212A (en) | High performance liquid chromatography detection method for hydroxylamine residue in medicine | |
| CN113484430B (en) | Method for measuring related substances of L-alanine isopropyl ester hydrochloride by adopting high performance liquid chromatography | |
| CN111679010B (en) | High performance liquid chromatography detection method for Ruideciclovir intermediate GS-441524 | |
| CN106525994B (en) | Method for determining related substances of paracetamol and tramadol capsule | |
| CN101658550A (en) | Method for measuring content of selfheal oral liquid | |
| CN114839287B (en) | Method for detecting sodium myristate in miboplatin | |
| CN113092624A (en) | Ruidexiwei-related substance and content determination method | |
| CN113820409B (en) | Method for detecting related substances in mother nucleus of moxifloxacin | |
| CN114113402B (en) | Method for measuring pinanediol content in bortezomib by adopting high performance liquid chromatography | |
| CN108760937B (en) | Determination of residual ethylenediamine in caspofungin acetate and application thereof | |
| CN114264765A (en) | Analysis method for determining related substances in glimepiride intermediate by using HPLC | |
| CN111579684A (en) | Method for measuring content of capsaicinoids in capsule wall material of capsule | |
| CN113686999B (en) | High performance liquid chromatography detection method for aniline residues in saccharide compounds | |
| CN112881538A (en) | Detection method for impurities and enantiomers in fudosteine and fudosteine tablets | |
| CN111323493A (en) | Method for detecting enantiomer of posaconazole starting material | |
| CN111175413B (en) | Method for detecting content of 4-chlorobutanol acetate in sulfobutyl-beta-cyclodextrin sodium raw material or preparation thereof | |
| CN113219105B (en) | Detection method of 2-nitro-4-methoxyaniline in esomeprazole magnesium and intermediate thereof | |
| CN109001337B (en) | Method for detecting polysaccharide content of mesona blume | |
| CN115480020B (en) | Method for measuring substance related to prionamine | |
| CN111650300B (en) | Method for measuring N, N-dimethylformamide and ethyl acetoacetate in coenzyme Q10 by gas chromatography |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |